FTLD-TDP With and Without GRN Mutations Cause Different Patterns of CA1 Pathology.
Frontotemporal lobar degeneration
Hippocampal sclerosis
Microglia
Neuroinflammation
Progranulin
TAR DNA-binding protein 43
Journal
Journal of neuropathology and experimental neurology
ISSN: 1554-6578
Titre abrégé: J Neuropathol Exp Neurol
Pays: England
ID NLM: 2985192R
Informations de publication
Date de publication:
01 09 2019
01 09 2019
Historique:
received:
23
03
2019
revised:
03
06
2019
accepted:
20
06
2019
pubmed:
31
7
2019
medline:
19
6
2020
entrez:
31
7
2019
Statut:
ppublish
Résumé
Heterozygous loss-of-function mutations in the GRN gene lead to progranulin (PGRN) haploinsufficiency and cause frontotemporal lobar degeneration with TDP-43 pathology type A (FTLD-TDP type A). PGRN is a highly conserved, secreted glycoprotein and functions in the central nervous system as a key modulator of microglial function. Hence, altered microglial function caused by PGRN deficiency may be tied to the pathogenesis of FTLD-TDP. Our previous studies showed that haploinsufficiency of GRN mutations extends to microglial PGRN expression in the hippocampal CA1 region. In this study, we found that the CA1 sector was associated with less neuronal loss and more frequent TDP-43 inclusions in FTLD-TDP type A cases with GRN mutations than in sporadic cases. In addition, the CA1 region in GRN mutation cases contained more rod-like microglia, which also had reduced PGRN expression. These findings suggest that the profile of TDP-43 inclusions, neuronal number, and microgliosis in the CA1 sector of FTLD-TDP type A cases may be influenced by GRN gene expression status.
Identifiants
pubmed: 31361008
pii: 5540708
doi: 10.1093/jnen/nlz059
pmc: PMC7967835
doi:
Substances chimiques
DNA-Binding Proteins
0
GRN protein, human
0
Progranulins
0
TARDBP protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
844-853Subventions
Organisme : NIA NIH HHS
ID : P30 AG013854
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056258
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC008552
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097261
Pays : United States
Informations de copyright
© 2019 American Association of Neuropathologists, Inc. All rights reserved.
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